转运紫杉醇的PLGA纳米粒对膀胱癌的细胞毒作用

Formulation of paclitaxel loaded PLGA nanoparticle and it＇s cytotoxicity on bladder cancer

目的研究可转运紫杉醇的多聚体纳米粒对膀胱癌的细胞毒作用。方法应用微乳化方法制备载紫杉醇的聚乳酸-羟基乙酸共聚物（PLGA）纳米粒，以聚乙烯醇（PVA）为表面稳定剂，并以转铁蛋白（Tf）表面修饰，分析纳米粒的大小、表面电荷、载药浓度、药物释放曲线以及空白纳米粒的安全性，观察紫杉醇溶液及载紫杉醇纳米粒对膀胱癌细胞系J-82的细胞毒作用。结果PVA纳米粒直径约200nm，Z电势约-24mV，载药浓度约6．5％（w／w），药物释放曲线为双相性。Tf表面修饰的纳米粒直径比PVA纳米粒稍大，z电势、载药浓度、药物释放曲线与PVA纳米粒相似。两种空白纳米粒不具有细胞毒性。紫杉醇溶液在50ng／ml时J-82细胞存活率为82．0％，100ng／ml时为36．0％。PVA纳米粒在50ng／ml和100ng／ml时细胞存活率分别为40．2％和15．8％，而Tf纳米粒分别为32．9％和7．2％，两种载药纳米粒抑制J-82细胞的作用明显强于紫杉醇溶液。结论PLGA纳米粒是安全有效的载药工具，可以明显增强紫杉醇对膀胱癌的细胞毒作用。

Objective To formulate paelitaxel loaded polymer nanoparticle and evaluate it＇s application in treatment of bladder. Methods Paelitaxel loaded Poly （lactide-eo-glyeolide） （PLGA） nanopartieles were formulated with mieroemulsion method, Polyvinyl alcohol（PVA） was used as surfaetant. Trans- ferrin （Tf） was used to modify the nanoparticles. The size, Z-potential, drug loading, drug release, cytotox- icity of bland nanopartieles and paelitaxel-loaded nanoparticles on bladder cancer cell line J^82 were meas- ured. Results The size of nanopartieles was about 200 nm, Z-potential was -24 mV, drug loading was about 6.5% （w/w） , cumulative drug release showed two phase curve. The size of Tf modified nanoparticles was a little bigger than no modified nanoparticles. The Z-potential, drug loading, drug release was similar. Two kinds of blank nanoparticles showed no cytotoxieity on bladder cancer cell line J-82. However, both paclitaxel-loaded nanoparticles had significantly higher cytotoxicity on J-82 compared to paclitaxel solution. Conclusions PLGA nanopartiele is a promising drug delivery vehicle, which could significantly improve the antieanccr effect of paclitaxel on bladder cancer.